CAJ | 학술논문

背景:核因子κB在转录水平调控着许多细胞因子、黏附因子的表达,在角膜移植排斥反应中可能起着中心调控作用.目的:观察核因子κB和细胞间黏附分子1、血管内皮生长因子在角膜植片中的动态表达规律以及环孢霉素A的干预作用.设计、时间及地点:随机对照动物实验,于2005-01/07在解放军第一军医大学珠江医院眼科完成.材料:选用健康清洁级SD大鼠40只及Wistar大鼠50只.随机分为3组:同基因移植组Wistar大鼠10只为供者,Wistar大鼠20只为受者;同种异体移植组Wistar大鼠10只为供者,SD大鼠20只为受者:同种异体移植+环孢霉素A治疗组Wistar大鼠10只为供者,SD大鼠20只为受者.方法:建立大鼠角膜移植模型,移植后所有受者术眼结膜下注射庆大霉素,隔日1次,每次2000U,共用3次;2.5 g/L氯霉素眼液滴眼,2次/d,每次2滴,连续用18d.50/L托品酰胺眼液滴眼,1次/d,每次2滴,连用1周.环孢霉素A治疗组移植后第1天开始用10g/L环孢霉素A眼液滴眼,3次/d,每次2滴,连续用18 d.主要观察指标:各组移植后3,7,12,18d测定角膜移植排斥反应指数评分,并于各时间点观察角膜植片病理学变化,检测核因子κB与细胞间黏附分子1、血管内皮生长因子的表达.结果:在观察期18 d内,同基因组未出现排斥反应,同种异体移植组在各时间点的排斥反应指数高于同基因移植组(P.<0.05),而同种异体移植+环孢霉素A治疗组排斥反应指数低于同种异体移植组(P<0.05).免疫组织化学结果显示:核因子κB与细胞间黏附分子1、血管内皮生长因子分布角膜上皮层、基质层及新生血管内皮细胞.各时间点,同种异体移植组角膜中核因子κB与细胞间黏附分子1、血管内皮生长因子的表达高于同基因移植组(P<0.05),而低于同种异体移植+环孢霉素A治疗组(P<0.05).结论:环孢霉素A通过减弱核因子κB核转位和发挥活性,抑制受其调控的多种细胞因子、黏附分子等移植排斥相关因子的表达,从而抑制角膜移植排斥反应的发生发展. 揹景:覈因子κB在轉錄水平調控著許多細胞因子、黏附因子的錶達,在角膜移植排斥反應中可能起著中心調控作用.目的:觀察覈因子κB和細胞間黏附分子1、血管內皮生長因子在角膜植片中的動態錶達規律以及環孢黴素A的榦預作用.設計、時間及地點:隨機對照動物實驗,于2005-01/07在解放軍第一軍醫大學珠江醫院眼科完成.材料:選用健康清潔級SD大鼠40隻及Wistar大鼠50隻.隨機分為3組:同基因移植組Wistar大鼠10隻為供者,Wistar大鼠20隻為受者;同種異體移植組Wistar大鼠10隻為供者,SD大鼠20隻為受者:同種異體移植+環孢黴素A治療組Wistar大鼠10隻為供者,SD大鼠20隻為受者.方法:建立大鼠角膜移植模型,移植後所有受者術眼結膜下註射慶大黴素,隔日1次,每次2000U,共用3次;2.5 g/L氯黴素眼液滴眼,2次/d,每次2滴,連續用18d.50/L託品酰胺眼液滴眼,1次/d,每次2滴,連用1週.環孢黴素A治療組移植後第1天開始用10g/L環孢黴素A眼液滴眼,3次/d,每次2滴,連續用18 d.主要觀察指標:各組移植後3,7,12,18d測定角膜移植排斥反應指數評分,併于各時間點觀察角膜植片病理學變化,檢測覈因子κB與細胞間黏附分子1、血管內皮生長因子的錶達.結果:在觀察期18 d內,同基因組未齣現排斥反應,同種異體移植組在各時間點的排斥反應指數高于同基因移植組(P.<0.05),而同種異體移植+環孢黴素A治療組排斥反應指數低于同種異體移植組(P<0.05).免疫組織化學結果顯示:覈因子κB與細胞間黏附分子1、血管內皮生長因子分佈角膜上皮層、基質層及新生血管內皮細胞.各時間點,同種異體移植組角膜中覈因子κB與細胞間黏附分子1、血管內皮生長因子的錶達高于同基因移植組(P<0.05),而低于同種異體移植+環孢黴素A治療組(P<0.05).結論:環孢黴素A通過減弱覈因子κB覈轉位和髮揮活性,抑製受其調控的多種細胞因子、黏附分子等移植排斥相關因子的錶達,從而抑製角膜移植排斥反應的髮生髮展.
배경:핵인자κB재전록수평조공착허다세포인자、점부인자적표체,재각막이식배척반응중가능기착중심조공작용.목적:관찰핵인자κB화세포간점부분자1、혈관내피생장인자재각막식편중적동태표체규률이급배포매소A적간예작용.설계、시간급지점:수궤대조동물실험,우2005-01/07재해방군제일군의대학주강의원안과완성.재료:선용건강청길급SD대서40지급Wistar대서50지.수궤분위3조:동기인이식조Wistar대서10지위공자,Wistar대서20지위수자;동충이체이식조Wistar대서10지위공자,SD대서20지위수자:동충이체이식+배포매소A치료조Wistar대서10지위공자,SD대서20지위수자.방법:건립대서각막이식모형,이식후소유수자술안결막하주사경대매소,격일1차,매차2000U,공용3차;2.5 g/L록매소안액적안,2차/d,매차2적,련속용18d.50/L탁품선알안액적안,1차/d,매차2적,련용1주.배포매소A치료조이식후제1천개시용10g/L배포매소A안액적안,3차/d,매차2적,련속용18 d.주요관찰지표:각조이식후3,7,12,18d측정각막이식배척반응지수평분,병우각시간점관찰각막식편병이학변화,검측핵인자κB여세포간점부분자1、혈관내피생장인자적표체.결과:재관찰기18 d내,동기인조미출현배척반응,동충이체이식조재각시간점적배척반응지수고우동기인이식조(P.<0.05),이동충이체이식+배포매소A치료조배척반응지수저우동충이체이식조(P<0.05).면역조직화학결과현시:핵인자κB여세포간점부분자1、혈관내피생장인자분포각막상피층、기질층급신생혈관내피세포.각시간점,동충이체이식조각막중핵인자κB여세포간점부분자1、혈관내피생장인자적표체고우동기인이식조(P<0.05),이저우동충이체이식+배포매소A치료조(P<0.05).결론:배포매소A통과감약핵인자κB핵전위화발휘활성,억제수기조공적다충세포인자、점부분자등이식배척상관인자적표체,종이억제각막이식배척반응적발생발전.
BACKGROUND: Nuclear factor-kappa B (NF-κB) plays a key role in regulating expressions of cytokines and adhesion factors during transcription and in central adjustment during corneal graft rejection reaction.OBJECTIVE: To study the dynamic expressions of NF-κB, intercellular adhesion molecular 1 (ICAM-1) and vascular endothelial growth factor (VEGF) in corneal graft and to investigate the interventional effect of cyclosporin A (CsA). DESIGN, TIME AND SETTING: A randomized controlled animal study was performed in the Department of Ophthalmology, Zhujiang Hospital, the First Military Medical University of Chinese PLA between January and July 2005.MATERIALS: 40 SD rats and 50 Wistar rats were included and randomly divided into three groups, syngenic transplantation (10 Wistar rats used as donor and another 20 Wistar rats used as acceptor), allogeneic transplantation (10 Wistar rats used as donor, and 20 SD rats used as acceptor), and allogeneic transplantation+CsA treatment (10 Wistar rats used as donor, and 20 SD rats used as acceptor).METHODS: Comeal transplantation models were established. Gentamicin (2 000 U) was subconjunctivally injected into the experimental eyes of all ecceptors every other day for three times in total; chloroptic (2.5 g/L) was then used two droplets every time, twice a day, and 18 successive days in total; additionally, tropicamide (5 g/L) was also used two droplets every time, once a day, and 7 successive days in total. One day after corneal transplantation, CsA eye droplet (10 g/L) was used in the allogeneic transplantation+CsA treatment group two droplets every time, three times a day, and 18 successive days in total.MAIN OUTCOME MEASURES: Scores of corneal graft rejection reaction index were measured at day 3, 7, 12, and 18 after corneal transplantation; pathological changes of corneal graft were observed at the same time points to detect expressions of NF-κB, ICAM-1, and VEGF.RESULTS: Rejection reaction was not observed in the syngenic transplantation group at 18 days; however, indexes of rejection reaction in the allogeneic transplantation group were higher than those in the syngenic transplantation group at four time points (P<0.05), but indexes in the allogeneic transplantation+CsA treatment group were lower than those in the allogeneic transplantation group (P<0.05). Immunohistochemical examination indicated that NF-κB, ICAM-1, and VEGF were located at corneal epithelial lamina and substantia propria layer and in newborn vascular endothelial cells. At each time point, expressions of NF-κB, ICAM-1, and VEGF in the allogeneic transplantation group were higher than those in the syngenic transplantation group (P<0.05) but lower than those in the allogeneic transplantation+CsA treatment group (P<0.05).CONCLUSION: CsA can weaken nuclear translocation and activity of NF-κB to inhibit expressions of cytokines, adhesion molecules, and other relative factors so as to inhibit ccurrence and development of corneal graft rejection reaction.